The overall goal of the proposed research is to assess the immunological response of humans to defined schistosome antigens. Such information will be valuable in the evaluation of the effects of immunization of drug treated (previously infected) individuals that exhibit various clinical forms of schistosomiasis and contribute to the answer for questions like 'who from endemic areas should be vaccinated?.' These studies are best performed on subjects from endemic areas, exposed to the parasite under natural conditions of transmission. Although experimental infections can provide important information, they are not able to reproduce the complex interactions between genetic, immunological and environmental factors that must be taken into account for the design of a vaccine. Our approach is to study well defined cohorts of individuals from endemic areas to address the following specific aims: (1) Study B and T cell response to defined antigens in clinically selected patients. The immune responses will be examined in patients with acute, intestinal, or hepatointestinal schistosomiasis before and after drug treatment. These results will be compared with similarly obtained results from endemic normals and non-endemic normals. (2) To determine if there is a bias in humoral and cellular immune responses to epitopes of selected antigens. This will be accompanied by determining the isotype of antibody that recognizes each epitope assessing the phenotype of the T cells that respond to each epitope. (3) Further elucidate the role of IgE and IgG4 in resistance/susceptibility to schistosome infection. (4) Determine HLA association within selected clinical forms of disease to compare with endemic normals that are egg negative but show in vitro responses to schistosome antigens. (5) Determine if there is variation in the human immune response to selected antigens obtained from different S mansoni isolates. The overall theme of this program project is to study human immune responses to schistosomiasis and Chagas disease. This project plays and integral role in the program as it provides data on the quality of human responses to defined antigens (epitopes) and attempts to answer questions about how humans with various previous exposures to schistosomiasis might respond to a defined antigen vaccine.